Benjamin Bearnot

Loss to Care and Death Before Antiretroviral Therapy in Durban, South Africa

Objective:To examine the loss to care and mortality rates before starting antiretroviral therapy (ART) among ART eligible HIV-infected patients in Durban, South Africa. Design:Retrospective cohort study. Methods:We reviewed data from ART eligible adults (≥18 years) at an urban HIV clinic that charges a monthly fee from July to December 2006. ART eligibility was based on CD4 count ≤200 cells per microliter or clinical criteria and a psychosocial assessment. Patients who did not start ART and were lost within 3 months were phoned. Correlates of loss to care were evaluated using logistic regression. Results:During the study period, 501 patients registered for ART training. Mean time from initial CD4 count to first ART training was 3.6 months (interquartile range 2.3-3.9 months). Four hundred eight patients (81.4%) were in care and on ART at 3-month follow-up, and 11 (2.2%) were in care but had not initiated ART. Eighty-two ART eligible patients (16.4%) were lost before ART initiation. Of these, 28 (34.1%) had died; two thirds of deaths occurred before or within 2 months after the first ART training. Despite multiple attempts, 32 patients (39%) were unreachable by phone. Lower baseline CD4 counts (≤100 cells/μL) and unemployment were independently associated with being lost. Conclusions:Loss to care and death occur frequently before starting ART at an HIV clinic in Durban, South Africa. This delay from CD4 count to ART training, even among those with the lowest CD4 counts, highlights the need for interventions that improve linkage to care and prioritize ART initiation for those with low baseline CD4 counts.

Gbeta5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells.

The time course of G‐protein‐coupled responses is largely determined by the kinetics of GTP hydrolysis by the G protein α subunit, which is accelerated by interaction with regulator of G‐protein signaling (RGS) proteins. Light responses of ON‐bipolar cells of the vertebrate retina require rapid inactivation of the G protein Gαo, which is activated in the dark by metabotropic glutamate receptor, mGluR6, in their dendritic tips. It is not yet known, however, which RGS protein(s) might be responsible for rapid inactivation kinetics. By immunofluorescence and co‐immunoprecipitation, we have identified complexes of the Gαo‐selective RGS proteins RGS7 and RGS11, with their obligate binding partner, Gβ5, that are localized to the dendritic tips of murine rod and cone ON‐bipolar cells, along with mGluR6. Experiments using pre‐ and post‐synaptic markers, and a dissociated bipolar cell preparation, clearly identified the location of these complexes as the ON‐bipolar cell dendritic tips and not the adjacent photoreceptor terminals or horizontal cell dendrites. In mice lacking mGluR6, the distribution of RGS11, RGS7 and Gβ5 shifts away from the dendritic tips, implying a functional relationship with mGluR6. The precise co‐localization of Gβ5–RGS7 and Gβ5–RGS11 with mGluR6, and the dependence of localization on the presence of mGluR6, suggests that Gβ5–RGS7 and Gβ5–RGS11 function specifically in the mGluR6 signal transduction pathway, where they may stimulate the GTPase activity of Gαo, thus accelerating the ON‐bipolar cell light response, in a manner analogous to the acceleration of photoreceptor light responses by the Gβ5–RGS9‐1 complex.

Linkage to care following community-based mobile HIV testing compared with clinic-based testing in Umlazi Township, Durban, South Africa†

The aim of the study was to assess HIV prevalence, disease stage and linkage to HIV care following diagnosis at a mobile HIV testing unit, compared with results for clinic‐based testing, in a Durban township.

Global Health Research in Narrative: A Qualitative Look at the FICRS-F Experience

For American professional and graduate health sciences trainees, a mentored fellowship in a low- or middle-income country (LMIC) can be a transformative experience of personal growth and scientific discovery. We invited 86 American trainees in the Fogarty International Clinical Research Scholars and Fellows Program and Fulbright-Fogarty Fellowship 2011-2012 cohorts to contribute personal essays about formative experiences from their fellowships. Nine trainees contributed essays that were analyzed using an inductive approach. The most frequently addressed themes were the strong continuity of research and infrastructure at Fogarty fellowship sites, the time-limited nature of this international fellowship experience, and the ways in which this fellowship period was important for shaping future career planning. Trainees also addressed interaction with host communities vis-à-vis engagement in project implementation. These qualitative essays have contributed insights on how a 1-year mentored LMIC-based research training experience can influence professional development, complementing conventional evaluations. Full text of the essays is available at http://fogartyscholars.org/.

Geospatial analysis of emergency department visits for targeting community-based responses to the opioid epidemic

The opioid epidemic in the United States carries significant morbidity and mortality and requires a coordinated response among emergency providers, outpatient providers, public health departments, and communities. Anecdotally, providers across the spectrum of care at Massachusetts General Hospital (MGH) in Boston, MA have noticed that Charlestown, a community in northeast Boston, has been particularly impacted by the opioid epidemic and needs both emergency and longer-term resources. We hypothesized that geospatial analysis of the home addresses of patients presenting to the MGH emergency department (ED) with opioid-related emergencies might identify “hot spots” of opioid-related healthcare needs within Charlestown that could then be targeted for further investigation and resource deployment. Here, we present a geospatial analysis at the United States census tract level of the home addresses of all patients who presented to the MGH ED for opioid-related emergency visits between 7/1/2012 and 6/30/2015, including 191 visits from 100 addresses in Charlestown, MA. Among the six census tracts that comprise Charlestown, we find a 9.5-fold difference in opioid-related ED visits, with 45% of all opioid-related visits from Charlestown originating in tract 040401. The signal from this census tract remains strong after adjusting for population differences between census tracts, and while this tract is one of the higher utilizing census tracts in Charlestown of the MGH ED for all cause visits, it also has a 2.9-fold higher rate of opioid-related visits than the remainder of Charlestown. Identifying this hot spot of opioid-related emergency needs within Charlestown may help re-distribute existing resources efficiently, empower community and ED-based physicians to advocate for their patients, and serve as a catalyst for partnerships between MGH and local community groups. More broadly, this analysis demonstrates that EDs can use geospatial analysis to address the emergency and longer-term health needs of the communities they are designed to serve.

Serial procalcitonin as a predictor of bacteremia and need for ICU care in adults with pneumonia, including those with highest severity: a prospective cohort study

Abstract Background Procalcitonin (PCT) is a prohormone that rises in bacterial pneumonia and has promise in reducing antibiotic use. Despite these attributes, there are inconclusive data on its use for clinical prognostication. We hypothesize that serial PCT measurements can predict mortality, intensive care unit (ICU) admission, and bacteremia. Methods A prospective cohort study of inpatients diagnosed with pneumonia was performed at a large tertiary care center in Boston, Massachusetts. Procalcitonin was measured on days 1 through 4. The primary endpoint was a composite adverse outcome defined as all-cause mortality, ICU admission, and bacteremia. Regression models were calculated with area under the receiver operating characteristic curve (AUC) as a measure of discrimination. Results Of 505 patients, 317 patients had a final diagnosis of community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP). Procalcitonin was significantly higher for CAP and HCAP patients meeting the composite primary endpoint, bacteremia, and ICU admission, but not mortality. Incorporation of serial PCT levels into a statistical model including the Pneumonia Severity Index (PSI) improved the prognostic performance of the PSI with respect to the primary composite endpoint (AUC from 0.61 to 0.66), bacteremia (AUC from 0.67 to 0.85), and need for ICU-level care (AUC from 0.58 to 0.64). For patients in the highest risk class PSI >130, PCT was capable of further risk stratification for prediction of adverse outcomes. Conclusion Serial PCT measurement in patients with pneumonia shows promise for predicting adverse clinical outcomes, including in those at highest mortality risk.

Access to Treatment for Alcohol Use Disorder at US Health Centers: a National Study

Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Tobacco Research and Treatment Center, Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Institute for Research, Quality, and Policy in Homeless Health Care, Boston Health Care for the Homeless Program, Boston, MA, USA.

Using Publicly Available Data to Understand the Opioid Overdose Epidemic: Geospatial Distribution of Discarded Needles in Boston, Massachusetts

Objectives To use publicly available, crowdsourced data to understand geospatial trends in discarded needles. Methods We completed multiple geospatial analyses of discarded needles reported through the Boston, Massachusetts, 311 service request system. Results Between May 2015 and August 2017, 4763 discarded needles were reported. The highest concentration of needles were reported in census block groups in the South End and Roxbury neighborhoods. Cumulatively, 78.3% of the needles were reported within 1 kilometer of methadone clinics, safe needle deposit sites, homeless shelters, or hospitals. Conclusions Publicly reported data can help identify hot spots of discarded needles and examine indicators of spatial association. In Boston, the number of discarded needles being reported is rising, with the highest density of needles found in 2 central neighborhoods with several outlying hot spots. Most needles were found near areas associated with social stress and substance use disorder. Public Health Implications. This analysis represents a novel way of leveraging publicly available information to target community responses to the opioid epidemic. Identifying hot spots of discarded needles may enable public health organizations to target future efforts to encourage safer needle disposal practices and reduce public injection drug use.

Serial Procalcitonin Levels Correlate with Microbial Etiology in Hospitalized Patients with Pneumonia

Abstract Background Procalcitonin (PCT) is a biomarker that is finding increasing diagnostic and prognostic utility in lower respiratory infections. It remains unclear, however, whether it can be helpful in predicting the bacterial etiology of pneumonia, with a view to informing antibiotic choice and duration. This study examines the relationship between serial PCT measurements and microbial etiology in patients hospitalized for pneumonia to determine whether changes in PCT levels provide discriminatory information on microbial etiology. Methods We performed a subgroup analysis of data from a prospective cohort study of 505 patients admitted to a tertiary care center with findings concerning for pneumonia. Microbial etiology of pneumonia was determined from high quality respiratory samples, blood cultures or other relevant diagnostic tests according to standard protocols. Procalcitonin levels were measured serially during the first four days of hospitalization. We compared procalcitonin levels between different bacterial etiologies over the first four days of admission, using the Mann–Whitney-U test to assess for statistical significance. Results Out of 505 patients, the diagnosis of pneumonia was adjudicated in 317, and bacterial etiology determined in 62 cases. The predominant pathogens were Staphylococcus aureus (N = 18), Streptococcus pneumoniae (N = 6), Pseudomonas aeruginosa (N = 11) and Haemophilus influenza (N = 5). Admission levels of PCT were lowest in Pseudomonas infections and highest in pneumococcal infections, though not reaching statistical significance. On hospital days two and three, pneumococcal procalcitonin levels were significantly higher than all other etiologies, but on day four, there was no statistically significant difference in PCT values for different microbial etiologies. Conclusion Serial procalcitonin levels during the early course of bacterial pneumonia reveal a difference between pneumococcal and other bacterial etiologies, and may have an adjunct role in guiding antibiotic choice and duration. Disclosures All authors: No reported disclosures.

Mitigation Strategies for Opioid Abuse.

The authors reply: We thank Kaplan et al. for calling attention to the description of hereditary vibratory angioedema in 19721 and the report in 1976 that the onset of this condition was associated with histamine release.2 We were aware of these studies and attempted to find contact information for any surviving members of the family that was described in these studies or similar patients with the intention of screening them for variants in ADGRE2, but we were unsuccessful. Despite the similar features and inheritance pattern shared by vibratory angioedema and vibratory urticaria, the two conditions are not clinically identical: the swelling in patients with vibratory angioedema persisted for hours to days,1 whereas the swelling in our cohort, including the patients with “dermo-distortive urticaria” described in 1981,3 resolved within 1 hour. Currently, the genetic basis of vibratory angioedema remains unknown, but we agree that ADGRE2 is an excellent candidate gene and propose that genetic variation in ADGRE2 or related genes may underlie a diversity of physical urticarias with similar molecular mechanisms. Steven E. Boyden, Ph.D.